Infection with HIV and SIV often result in intestinal disease characterized clinically by diarrhea and wasting, and morphologically by intestinal villus blunting and fusion. Often, no opportunistic or secondary pathogens are identified in these patients and it is hypothesized that primary infection with HIV/SIV is responsible for these functional and morphological alterations. To rigorously examine physiologic alterations that occur in the intestine during primary SIV infection, we have begun examining intestinal segments in ssing chambers. ssing chambers are the "gold standard for characterizing the physiology of the intestine in a rigorous, quantitative fashion. We have examined the duodenum, jejunum, and ileum from five normal and ten SIV-infected macaques and determined that marked perturbations in intestinal resistance, secretion, and permeability occur within the first few days after infection with SIVmac239. Furthermore, these alterations are most severe in the ileum, which has the highest concentration of lymphocytes, suggesting that the alterations in intestinal function and permeability are directly related to perturbations in gut-associated lymphoid tissue.